细菌热休克蛋白60可能通过激活丝裂原活化蛋白激酶和抑制α6β4整合素表达来增加上皮细胞迁移。

Bacterial heat shock protein 60 may increase epithelial cell migration through activation of MAP kinases and inhibition of alpha6beta4 integrin expression.

作者信息

Zhang Liangxuan, Koivisto Leeni, Heino Jyrki, Uitto Veli-Jukka

机构信息

Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.

出版信息

Biochem Biophys Res Commun. 2004 Jul 9;319(4):1088-95. doi: 10.1016/j.bbrc.2004.04.202.

DOI:10.1016/j.bbrc.2004.04.202

PMID:15194479

Abstract

Exogenous heat shock proteins may modify cell behavior of infected epithelium. The effect of heat shock protein 60 (hsp60) of Actinobacillus actinomycetemcomitans and Escherichia coli, and human recombinant hsp60 on migration of HaCaT skin keratinocytes was studied using the Boyden chamber assay. Hsp60 from different species increased cell migration by two- to fivefold and this effect was inhibited by ERK inhibitor PD 98059, p38 inhibitor SB 203580, and a function-blocking epidermal growth factor receptor (EGFR) antibody. Hsp60 reduced the expression of alpha6-integrin mRNA and its protein levels on the cell surface but had no effect on the expression of beta4, beta1, alpha1, alpha5 or alphav integrin subunits. Hsp60 also significantly inhibited cell adhesion to laminin-5, a ligand of alpha6beta4 integrin. These results suggest that exogenous hsp60 released from bacteria or inflammatory cells may promote epithelial cell migration through activation of EGFR and MAP kinases, and inhibition of alpha6beta4 integrin expression.

摘要

外源性热休克蛋白可能会改变受感染上皮细胞的行为。利用博伊登小室试验研究了伴放线放线杆菌和大肠杆菌的热休克蛋白60（hsp60）以及人重组hsp60对HaCaT皮肤角质形成细胞迁移的影响。来自不同物种的hsp60使细胞迁移增加了2至5倍，且这种作用被ERK抑制剂PD 98059、p38抑制剂SB 203580以及一种功能阻断性表皮生长因子受体（EGFR）抗体所抑制。Hsp60降低了α6整合素mRNA的表达及其在细胞表面的蛋白质水平，但对β4、β1、α1、α5或αv整合素亚基的表达没有影响。Hsp60还显著抑制细胞与层粘连蛋白-5（α6β4整合素的一种配体）的黏附。这些结果表明，从细菌或炎症细胞释放的外源性hsp60可能通过激活EGFR和丝裂原活化蛋白激酶以及抑制α6β4整合素表达来促进上皮细胞迁移。